Testosterone and 5α-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines
Testosterone and 5α-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines
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DOI：
10.1080/713603030
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发表时间：
2002-04-01
影响因子：
2
通讯作者：
Rabe, T
中科院分区：
文献类型：
--
作者：
Ortmann, J;Prifti, S;Rabe, T
雄激素对女性乳腺癌的生长和发展具有生物学和临床重要性，雄激素受体（AR）已被证明是肿瘤分化的预测因子。在本研究中，我们研究了AR状态与睾酮和5 α-二氢睾酮（DHT）依赖的人乳腺癌细胞系MCF-7，T47-D，MDA-MB 435 S和BT-20的增殖之间的关系。AR状态通过免疫细胞化学和Western印迹分析进行了研究。所有四种细胞系均对AR呈阳性染色。Western blot分析显示，与BT-20细胞相比，MCF-7细胞中AR的强表达。根据增殖动力学，我们在所有四种细胞系中观察到睾酮和DHT处理对细胞生长的显著（p小于或等于0.05）剂量依赖性抑制。在雌激素受体（ER）阴性细胞系BT-20和MDA-MB 435 S中，睾酮是比DHT更有效的细胞增殖抑制剂（p小于或等于0.05），与ER阳性细胞系MCF-7和T47-D相反，其中DHT实现了更强的增殖抑制。雌激素受体阳性细胞中睾酮向雌激素的部分转化可能是这种效应的一种解释。我们的数据支持雄激素在乳腺癌生长调节中的可能作用。需要临床研究来分析AR作为乳腺癌内分泌治疗反应的可能预测因子的重要性。
Androgens are of biological and clinical importance for the growth and development of breast cancer in women, and the androgen receptor (AR) has been shown to be a predictor of tumor differentiation. In the present study, we investigated the relationship between AR status and testosterone and 5alpha-dihydrotestosterone (DHT)-dependent proliferation of the human breast carcinoma cell lines MCF-7, T47-D, MDA-MB 435S and BT-20. AR status was studied by means of immunocytochemistry and Western blot analysis. All four cell lines stained positively for AR. Western blot analysis revealed a strong expression of AR in MCF-7, in contrast to BT-20 cells. According to proliferation kinetics, we observed a significant (p less than or equal to 0.05) dose-dependent inhibition of cell growth by testosterone and DHT treatment in all four cell lines. In the estrogen receptor (ER)-negative cell lines BT-20 and MDA-MB 435S, testosterone was a more potent inhibitor of cell proliferation than DHT (p less than or equal to 0.05), in contrast to the ER-positive cells lines MCF-7 and T47-D, in which a stronger inhibition of proliferation was achieved by DHT. A partial transformation Of testosterone to estrogen in ER-positive cells might be an explanation for this effect. Our data favor a possible role of androgens in growth regulation of breast cancer. Clinical studies are needed to analyze the importance of AR as a possible predictor in response to endocrine therapy of breast cancer.